Cellular deconvolution is a valuable computational process that can infer the cellular composition of heterogeneous tissue samples from bulk RNA-sequencing data. Benchmark testing is a crucial step ...in the development and evaluation of new cellular deconvolution algorithms, and also plays a key role in the process of building and optimizing deconvolution pipelines for specific experimental applications. However, few in vivo benchmarking datasets exist, particularly for whole blood, which is the single most profiled human tissue. Here, we describe a unique dataset containing whole blood gene expression profiles and matched circulating leukocyte counts from a large cohort of human donors with utility for benchmarking cellular deconvolution pipelines.
To produce this dataset, venous whole blood was sampled from 138 total donors recruited at an academic medical center. Genome-wide expression profiling was subsequently performed via next-generation RNA sequencing, and white blood cell differentials were collected in parallel using flow cytometry. The resultant final dataset contains donor-level expression data for over 45,000 protein coding and non-protein coding genes, as well as matched neutrophil, lymphocyte, monocyte, and eosinophil counts.
CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with ...lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.
Long-distance terrestrial migrations are imperiled globally. We determined both round-trip migration distances (straight-line measurements between migratory end points) and total annual movement (sum ...of the distances between successive relocations over a year) for a suite of large mammals that had potential for long-distance movements to test which species displayed the longest of both. We found that caribou likely do exhibit the longest terrestrial migrations on the planet, but, over the course of a year, gray wolves move the most. Our results were consistent with the trophic-level based hypothesis that predators would move more than their prey. Herbivores in low productivity environments moved more than herbivores in more productive habitats. We also found that larger members of the same guild moved less than smaller members, supporting the 'gastro-centric' hypothesis. A better understanding of migration and movements of large mammals should aid in their conservation by helping delineate conservation area boundaries and determine priority corridors for protection to preserve connectivity. The magnitude of the migrations and movements we documented should also provide guidance on the scale of conservation efforts required and assist conservation planning across agency and even national boundaries.
A central question in ecology is how to link processes that occur over different scales. The daily interactions of individual organisms ultimately determine community dynamics, population ...fluctuations and the functioning of entire ecosystems. Observations of these multiscale ecological processes are constrained by various technological, biological or logistical issues, and there are often vast discrepancies between the scale at which observation is possible and the scale of the question of interest. Animal movement is characterized by processes that act over multiple spatial and temporal scales. Second-by-second decisions accumulate to produce annual movement patterns. Individuals influence, and are influenced by, collective movement decisions, which then govern the spatial distribution of populations and the connectivity of meta-populations. While the field of movement ecology is experiencing unprecedented growth in the availability of movement data, there remain challenges in integrating observations with questions of ecological interest. In this article, we present the major challenges of addressing these issues within the context of the Serengeti wildebeest migration, a keystone ecological phenomena that crosses multiple scales of space, time and biological complexity.
This article is part of the theme issue 'Collective movement ecology'.
Retinal photoreceptors entrain the circadian system to the solar day. This photic resetting involves cAMP response element binding protein (CREB)-mediated upregulation of Per genes within individual ...cells of the suprachiasmatic nuclei (SCN). Our detailed understanding of this pathway is poor, and it remains unclear why entrainment to a new time zone takes several days. By analyzing the light-regulated transcriptome of the SCN, we have identified a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. SIK1 then inhibits further shifts of the clock by phosphorylation and deactivation of CRTC1. Knockdown of Sik1 within the SCN results in increased behavioral phase shifts and rapid re-entrainment following experimental jet lag. Thus SIK1 provides negative feedback, acting to suppress the effects of light on the clock. This pathway provides a potential target for the regulation of circadian rhythms.
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•Nocturnal light induces widespread transcriptional changes in the SCN•The CRTC1-SIK1 cascade regulates entrainment of the circadian clock•Negative feedback by SIK1 limits the effects of light on the clock•Homeostatic regulation of entrainment ensures gradual adaptation to a new time zone
A negative-feedback loop involving the kinase SIK1 and the transcriptional coactivator CRTC1 delays re-entrainment of the circadian clock to new time zones, causing jet lag. Remarkably, inhibition of SIK1 allows rapid re-entrainment after an experimental jet lag protocol in mice.
Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early ...expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging. Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission. We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype. Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.
Background
Vitamin D has immune‐modulating effects. We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory ...illness presentations.
Methods
A randomized, double‐blind, placebo‐controlled parallel‐group trial. We assigned pregnant women, from 27‐week gestation to birth, and then their infants, from birth to 6 months, to placebo or one of two dosages of daily oral vitamin D. Woman/infant pairs were randomized to: placebo/placebo, 1000 IU/400 IU or 2000 IU/800 IU. When the children were 18 months old, we measured serum‐specific IgE antibodies and identified acute primary care visits described by the doctor to be due to a cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough.
Results
Specific IgE was measured on 185 of 260 (71%) enrolled children. The proportion of children sensitized differed by study group for four mite antigens: Dermatophagoides farinae (Der‐f1, Der‐f2) and Dermatophagoides pteronyssinus (Der‐p1, Der‐p2). With results presented for placebo, lower dose, and higher dose vitamin D, respectively (all P < 0.05): Der‐f1 (18%, 10%, 2%), Der‐f2 (14%, 3%, 2%), Der‐p1 (19%, 14%, 3%) and Der‐p2 (12%, 2%, 3%). There were study group differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, P = 0.002), but not for the other respiratory diagnoses.
Conclusions
Vitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed.
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from ...asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.
New satellite remote sensing and machine learning techniques offer untapped possibilities to monitor global biodiversity with unprecedented speed and precision. These efficiencies promise to reveal ...novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Here, we present a robust transferable deep learning pipeline to automatically locate and count large herds of migratory ungulates (wildebeest and zebra) in the Serengeti-Mara ecosystem using fine-resolution (38-50 cm) satellite imagery. The results achieve accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types, with an overall F1-score of 84.75% (Precision: 87.85%, Recall: 81.86%). This research demonstrates the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. We also discuss the potential for satellite-derived species detections to advance basic understanding of animal behavior and ecology.
As an ecotoxicological tool, bioassays are an effective screening tool to eliminate plants sensitive to the contaminant of interest, and thereby reduce the number of plant species requiring further ...study. We conducted a bioassay analysis of fifteen plant species to determine their tolerance to diesel fuel toxicity. Dose-response analysis revealed that increasing diesel fuel concentrations in the soil generally led to a monotonically decreasing biomass in 13 species (P < 0.001), with EC10 values (±SE) ranging from 0.36 ± 0.18 g/kg to 12.67 ± 2.13 g/kg. On the other hand, hydrocarbons had a statistically significant hormetic influence on Medicago sativa (f = 3.90 ± 1.08; P < 0.01). The EC10 and EC50 values (±SE) from the fitted hormetic model were 15.33 ± 1.47 g/kg and 26.89 ± 2.00 g/kg, respectively. While previous studies have shown M. sativa’s tolerance of hydrocarbon toxicity, this is the first attempt to describe diesel fuel-induced hormesis in M. sativa using the Cedergreen-Ritz-Streibig model. This study thus shows that hormesis cannot be ignored in plant toxicology research, and that when present, an appropriate statistical model is necessary to avoid drawing wrong conclusions.
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•Hormesis cannot be ignored in plant ecotoxicology research.•Diesel fuel had a concentration-dependent monotonic impact on most species, but had a hormetic effect on Medicago sativa.•An appropriate dose-response model is crucial for the accurate assessment of hormesis in plants.•A wrong statistical model leads to a wrong interpretation of the potential of species for environmental remediation.
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